Influence of an Acidic Beverage on the Imatinib Exposure After Major Gastrectomy

NCT02185937 | Terminated Phase 1

• 1 other identifier: ABILITY
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The most common sites for GIST to occur are the stomach (60-70%) and proximal small intestines (20-25%). Therefore patients with GIST often have altered GI-tract due to tumor resection or palliative surgery which might affect imatinib exposure. Indeed, Yoo et al. showed that steady state imatinib trough levels in patients with advanced GISTs after major gastrectomy are lower compared to patients with a previous wedge resection or without gastric surgery. Patients that underwent major gastrectomy had an average imatinib plasma trough levels below 1000 µg/L. This while imatinib trough levels above 1000 µg/L are correlated to more beneficial treatment out-comes (longer Progression Free Survival). Since imatinib easily and rapidly dissolves at pH 5.5 or less, a lack of gastric acid secretion might be causing the decreased exposure in the patients that underwent major gastrectomy. Therefore the investigators would like to study if the exposure to imatinib in patients after major gastrectomy can be improved by creating a more acidic environment for absorption through combining imatinib intake with Coca-Cola.

Conditions

Gastrointestinal Stromal Tumor; Major Gastrectomy

Keywords

imatinib; gastrectomy; gastrointestinal stromal tumor; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• imatinib area under the curve

  imatinib exposure assessed as area under the curve

  day 7; predose - 10 hours after dosing

Secondary Outcomes (1)

• number of adverse events

  2 weeks

Study Arms (2)

water

NO INTERVENTION

imatinib intake with water

cola

ACTIVE COMPARATOR

imatinib intake with cola

Dietary Supplement: cola

Interventions

cola DIETARY_SUPPLEMENT

imatinib intake with coca-cola

Also known as: Coca-cola

cola

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients ≥ 18 years of age
• Patients with GIST, who previously underwent major gastrectomy
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1
• Already selected to receive imatinib therapy in a dose of 400-800mg imatinib daily, as judged by the treating physician and with respect for and in agreement with the registration guidelines
• Subject is able and willing to sign the Informed Consent Form prior to screening

You may not qualify if:

• Concomitant administration of any anti-cancer therapies (e.g. chemo-therapy, other targeted therapy, experimental drug, etc) other than imatinib
• Concomitant use of medication which strongly inhibits or induces CYP3A4
• Refractory nausea and vomiting, malabsorption with other causes than gastrectomy or external biliary shunt that would preclude adequate absorption.
• Unwillingness to use Coca-Cola
• Unwillingness or inability to swallow whole tablets
• Inability to comply with the requirements of the protocol
• Inability to understand the nature and extent of the study and the procedures required
• Participation in a drug study within 60 days prior to the first day of this study

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Radboudumc

Nijmegen, Netherlands

Location

Related Publications (1)

• Lubberman FJE, Gelderblom H, Wilmer CM, Kweekel DM, Desar IME, Colbers A, Burger D, van der Graaf WTA, van Erp N. Does a glass of Coke boost the exposure to imatinib in gastrointestinal stromal tumour patients after gastrectomy? Br J Clin Pharmacol. 2017 Oct;83(10):2312-2314. doi: 10.1111/bcp.13333. Epub 2017 Jul 4. No abstract available.

  PMID: 28677263 RESULT

MeSH Terms

Conditions

Gastrointestinal Stromal Tumors

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Study Officials

• Nielka van Erp

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2014
• First Posted: July 10, 2014
• Study Start: August 1, 2014
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: December 8, 2020

Record last verified: 2020-12

Locations

NL (1)